In 1869 Rutherford became Asst. Professor of Physiology at King's College, London. In 1871 he was appointed Professor of Physiology at the Royal Institution In 1874 he returned to Edinburgh University to succeed Bennett as Professor of Physiology there.[2]

Rutherford lectured at the University of Edinburgh when Arthur Conan Doyle studied medicine there. Like his fictional character Sherlock Holmes, who was based on a real person, Conan Doyle's Professor Challenger was based on Rutherford.

He died 21 February 1899 at 114 Douglas Crescent, Edinburgh and his body was buried at Ancrum.[3]

Richards, Stewart (May 1986). "Conan Doyle's 'Challenger' Unchampioned: William Rutherford, F.R.S. (1839–99), and the Origins of Practical Physiology in Britain". Notes and Records of the Royal Society of London (The Royal Society of London) 40 (2): 193–217. doi:10.1098/rsnr.1986.0011. JSTOR531688. PMID11620895.